The present invention relates generally to compositions and methods for treating hypertension; more specifically, it relates to methods and compositions for treating or preventing hypertension whereby the many and varied problems associated with the disease can be prevented, arrested, substantially alleviated, or cured by the submucosal delivery of a pharmaceutically acceptable base and an effective amount of at least one cannabinoid- or endocannabinoid-containing extract of a cloned hybrid of the plant Cannabis sativa, subspecies sativa and Cannabis sativa, subspecies indica of the CTS-X-ISS lineage.
Cannabis boasts a long and pertinent history of medicinal use, based in the earliest known civilizations. The first recorded use of medical cannabis dates back to 2800 B.C., when the Chinese Emperor Shen-nung used it as a muscle relaxant and painkiller. The ancient Egyptians also found medical benefits in cannabis, as evidenced by their usage of it to quell the pangs of childbirth. Numerous other civilizations, including the Assyrians, Persians, Zulu, Spaniards, and countless others, have since established traditional medical applications of cannabis. Underlying this historical trend is the simple fact that the medical benefits of marijuana have, and continue to serve, numerous cultures.
In America, over one hundred articles recommending cannabis were published between 1840 and 1900 alone. Cannabis was among the handful of drugs listed in The Pure Food and Drug Act of 1906, effectuating the Agreement for Unification of Pharmacopeial Formulas for Potent Drugs (see Treaty Series 510, 1906), and was considered at the time to be the most daunting intrusion by federal authorities into interstate commerce. Although other federal agencies could regulate prices and occupational safety, the USDA then became engaged in the regulation of the very manufacture and sale of products, in addition to advertising. The Pure Food and Drug Act required only that certain specified drugs, including alcohol, cocaine, heroin, morphine, and cannabis, be accurately labeled with contents and dosage. Previously, many drugs had been sold as patent medicines with secret ingredients or misleading labels. Cocaine, heroin, cannabis, and other such drugs continued to be legally available without prescription as long as they were labeled. It is estimated that sale of patent medicines containing opiates decreased by 33% after labeling was mandated. Two subsequent laws, the Food, Drug, and Cosmetic Act of 1938 and the 1962 Kefauver-Harris Amendments, strengthened the 1906 act's legacy of empowering the FDA. Ironically, the Pure Food and Drug Act of 1906 is cited by drug policy reform advocates such as James P. Gray as a successful model for re-legalization of currently prohibited drugs by requiring accurate labels, monitoring of purity and dose, and consumer education.
Cannabis continued to play a prominent part of the pharmacopoeia from 1870 up until 1937, when the Marijuana Tax Act effectively banned the plant from public consumption regardless of intended use. Employed primarily as a painkiller during childbirth, as a treatment for asthma and gonorrhea symptoms, and as a relaxant for anxiety-prone patients, marijuana was formerly a well-documented drug in standard texts on pharmacology and therapeutics. When Congress first considered banning the cannabis plant, the respected American Medical Association (AMA) testified before federal committees in defense of marijuana's medical applicability. Despite the AMA's efforts, the political motivations behind outlawing the plant far outweighed any medical considerations, and in 1937, cannabis became illegal. The sudden and severe public reaction to this “new” drug was surprising, considering that no one in America had even heard the word “marijuana” until the late 1920s. Akhavan, K, Marinol vs. Marijuana: Politics, Science, and Popular Culture, The American Alliance for Medical Cannabis (1997).
While the medical use of marijuana has been well known for decades, it remained illegal based on its federal Class I scheduling until 1996 when California enacted Proposition 215, the first state law that permitted its medical use with a recommendation by a physician. Tetrahydrocannabinol (THC) alone does not provide the benefits of the other cannabinoids found in various strains; the limitations of formulations to a liquid or pill create difficulties for patients attempting to titrate the optimal dose for their various conditions.
Today, the benefits of Cannabis in a variety of medical conditions are so well established that they have been enacted into statute in fourteen states: Alaska, California, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Jersey, New Mexico, Oregon, Rhode Island, Vermont and Washington. In California, Cannabis is deemed useful for cancer, anorexia, AIDS, chronic pain, spasticity, glaucoma, arthritis, migraine, or any other illness for which it provides relief. Section 11362.5 was added to the Health and Safety Code (b)(1)(A). In Nevada, NRS 453A.050 applies to a similar list of “Chronic or debilitating medical conditions” defined as 1)
Acquired immune deficiency syndrome; 2) Cancer; 3) Glaucoma; 4) A medical condition or treatment for a medical condition that produces, for a specific patient, one or more of the following: (a) Cachexia; (b) Persistent muscle spasms, including, without limitation, spasms caused by multiple sclerosis; c) Seizures, including, without limitation, seizures caused by epilepsy; (d) Severe nausea; or (e) Severe pain; or 5) Any other medical condition or treatment for a medical condition that is (a) Classified as a chronic or debilitating medical condition by regulation of the Division; or (b) Approved as a chronic or debilitating medical condition pursuant to a petition submitted in accordance with NRS 453A.710.
The etiology of glaucoma is an interruption to the normal outflow of aqueous humour within the chamber of the eye leading to elevated intra ocular pressure. As pressure rises, the optic nerve suffers irreversible damage, leading to a reduction in the field of vision and, ultimately, loss of eyesight. The most common type, chronic open-angle glaucoma, usually affects people over the age of 40, when the trabecular meshwork at the margins of the eye gradually becomes blocked and drainage slows. Cannabis indica and sativa have been used for many decades in glaucoma; for many patients is the only means to preserve their sight.
However, the benefits of Cannabis in other conditions associated with arteriolar constriction, though documented, are not as well known as in the case of glaucoma, some of the victims of which can find relief with no other medicine.
In an effort to provide the medical benefits of the plant, the drug dronabinol, Marinol®, a synthetic tetrahydrocannabinol (THC), once believed to be the active and therapeutic component of Cannabis, was introduced in 1985. Dronabinol is the subject of fourteen (14) patents, including use as an anti-emetic, U.S. Pat. No. 5,310,561, to Jao, et al, as an appetite stimulant, U.S. Pat. No. 6,703,418, to Plasse, and treatment for dementia, U.S. Pat. No. 5,804,592, to Volicer. U.S. Pat. No. 7,025,992, to Whittle discloses a Cannabis-based pharmaceutical formulation “for use in administration via a mucosal surface” which comprises both the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC), or the cannabinoids, tetrahydrocannabinovarin (THCV) and cannabidivarin (CBDV). The formulation is in a liquid dosage form producing particles having a mean aerodynamic particle size between 15 and 45 microns. Formulations suitable for oral administration can consist of (a) liquid solutions, such as an effective amount of Cannabis dissolved in diluents, such as water, oil, or saline, (b) capsules, sachets or tablets, each containing a predetermined amount of the active ingredient, as solids or granules, c) suspensions in an appropriate liquid, and (d) suitable emulsions. Tablet forms can include one or more of lactose, mannitol, corn starch, potato starch, microcrystalline cellulose, acacia, gelatin, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, stearic acid, and other excipients, colorants, diluents, buffering agents, moistening agents, preservatives, flavoring agents, and pharmacologically compatible carriers. Lozenge forms can comprise the active ingredient in a flavor, usually sucrose and acacia or tragacanth, as well as pastilles comprising the active ingredient in an inert base, such as gelatin and glycerin or sucrose and acacia emulsions, gels, and the like containing, in addition to the active ingredient, such carriers as are known in the art. Whittle, however, does not disclose a hybrid cross of Cannabis sativa, ssp. sativa and C. s. ssp. indica of the CTSX-ISS lineage specifically developed for its anti-hypertensive properties.
Hampson, U.S. Pat. No. 6,630,507, of the United States Department of Health and Human Services, discloses cannabinoid derivatives that protect the brain from anoxic damage induced by the neuronal release of the neurotransmitter glutamate, which stimulates NMDA (N-methyl-D-aspartate), AMPA (.alpha.-amino-3-hydroxy-5-methyl-4-isoxazole propionate) and kainate receptors, and resultant calcium influx into the neurons and production of reactive oxygen species.